Prevalence of preclinical Alzheimer disease

Abstract

ObjectiveTo determine the prevalence of preclinical Alzheimer disease (AD) according to current classification systems by examining CSF from a representative general population sample of 70-year-olds from Gothenburg, Sweden.MethodThe sample was derived from the population-based H70 Gothenburg Birth Cohort Studies in Gothenburg, Sweden. The participants (n = 322, age 70 years) underwent comprehensive neuropsychiatric, cognitive, and somatic examinations. CSF levels of β-amyloid (Aβ)42, Aβ40, total tau, and phosphorylated tau were measured. Preclinical AD was classified according to criteria of the A/T/N system, Dubois 2016, National Institute on Aging–Alzheimer's Association (NIA-AA) criteria, and International Working Group-2 (IWG-2) criteria. Individuals with Clinical Dementia Rating score >0 were excluded, leaving 259 cognitively unimpaired individuals.ResultsThe prevalence of amyloid pathology was 22.8%, of total tau pathology was 33.2%, and of phosphorylated tau pathology was 6.9%. With the A/T/N system, the prevalence of A+/T−/N− was 13.1%, A+/T−/N+ was 7.3%, A+/T+/N+ was 2.3%, A−/T−/N+ was 18.9%, and A−/T+/N+ was 4.6%. When the Dubois criteria were applied, the prevalence of asymptomatic at risk for AD was 36.7% and of preclinical AD was 9.7%. With the NIA-AA criteria, the prevalence of stage 1 was 13.1% and stage 2 was 9.7%. With the IWG-2 criteria, the prevalence of asymptomatic at risk for AD was 9.7%. The APOE ε4 allele was associated with several of the categories. Men more often had total tau pathology, A+/T−/N+, preclinical AD according to Dubois 2016, asymptomatic at risk for AD according to the IWG-2 criteria, and NIA-AA stage 2.ConclusionThe prevalence of pathologic AD markers was very common (46%) in a representative population sample of 70-year-olds. The clinical implications of these findings need to be scrutinized further in longitudinal studies.

Influence of the Mediterranean and Ketogenic Diets on Cognitive Status and Decline: A Narrative Review

“…Alzheimer's disease (AD), the most common cause of dementia [6], is characterized by the accumulation of amyloid β (Aβ) and hyper-phosphorylation of the Tau protein, with additional reduced acetylcholine levels and cerebral blood flow [2,7]. Furthermore, modifications in the blood-brain barrier (BBB), oxidative stress, mitochondrial impairment, neuroinflammation, and alterations in the insulin signaling have been observed in this condition [8].…”

Use of Biomarkers in Ongoing Research Protocols on Alzheimer’s Disease

“…In particular, the “real world” transferability of interventions emerging as effective in restricted samples of asymptomatic individuals with positive biomarkers will hardly be sustainable for our healthcare systems. Pathological AD markers are very common (i.e., 46%) in representative samples of older people [ 21 ], and it has been estimated that about 46.7 million Americans had preclinical AD in 2017 [ 22 ]. So, how can we translate these procedures on such a large scale to identify candidates for future disease-modifying treatments?…”

ADSoluble aggregates present in cerebrospinal fluid change in size and mechanism of toxicity during Alzheimer’s disease progression

“…MCI (6) and control (6) samples were collected from the Gothenburg H70 Birth Cohort Studies in Gothenburg, Sweden 14,36 . These samples were obtained from the Swedish Population Registry and included both persons living in private households and in residential care and approved by the Regional Ethical Review Board in Gothenburg.…”

“…CSF is continuously produced, recycled and freely exchanged with the interstitial fluid in the brain, making it an ideal reservoir of soluble aggregates that can be reflective of toxic species present in the brain tissue for that disease stage. It has been demonstrated that soluble Aβ is secreted into the CSF, making it an ideal biomarker candidate for AD 11,14,15 . Although the concentrations of Aβ oligomers and monomers have been measured in AD CSF, due to a lack of suitably sensitive methods, the specific detection and quantification of the heterogeneity in morphology of soluble Aβ aggregates present in CSF have not yet been determined.…”

“…assessments of episodic memory (short-term, long-term), aphasia, apraxia, agnosia, executive functioning and personality changes. Key informant interviews were performed by psychiatric research nurses as described previously14,36 .Examinations included the Mini Mental StateExamination and the clinical dementia rating (CDR). Dementia was diagnosed according to the DSM-III-R criteria.…”